a phase i, multicenter, dose escalation study of cat-8015 in patients with non-hodgkin's lymphoma (nhl)

Conditions: Lymphoma

Summary: a dose-escalation study to estimate the maximum tolerated dose(mtd) of cat-8015 that can be safely administered to a patient.

to estimate the maximum tolerated dose (mtd), defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on mtd, for subsequent clinical testing.

Eligibility criteria:
inclusion criteria: subjects must meet all of the following criteria to be eligible to participate in the study: * confirmed diagnosis of b-cell non-hodgkin's lymphoma * measurable disease * evidence of cd22-positive malignancy by the following criteria, \> 30% of malignant cells from a disease site cd22+ by facs analysis or, \> 15% of malignant cells from a disease site must react with anti-cd22 by immunohistochemistry * disease characteristics: patients with indolent subtypes of cd22+ b-cell non- hodgkin's lymphoma, including, but not limited to mantle cell lymphoma, follicular lymphoma and waldenström's macroglobulinemia, are eligible if stage iii-iv. if stage iii-iv. patients must have failed at least two or more courses of prior standard chemotherapy and/or biologic therapy (e.g. rituxan). patients with progressive mantle cell lymphoma may be eligible if they have failed one prior standard therapeutic regimen. * ecog performance status of 0-2 * patients with other cancers who meet eligibility criteria and have less than 5 years of disease free survival will be considered on a case-by-case basis * life expectancy of less than 6 months, as assessed by the principal investigator * must be able to understand and sign informed consent * must be at least 18 years old * female and male patients must agree to use an approved method of contraception during the study exclusion criteria: subjects meeting any of the following criteria are not eligible for participation in the study: * history of allogeneic bone marrow transplant * documented and ongoing central nervous system involvement with their malignant disease (history of cns involvement is not an exclusion criterion) * pregnant or breast-feeding females * hiv positive serology (due to increased risk of severe infection and unknown interaction of cat-8015 with antiretroviral drugs) * hepatitis b surface antigen positive * uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements * patients whose plasma contains either a significant level of antibody to cat-8015 as measured by elisa, or antibody that neutralizes the binding of cat-8015 to cd22 as measured by a competition elisa. hepatic function serum transaminases (either alt or ast) or bilirubin: * ≥ grade 2, unless bilirubin is due to gilbert's disease renal function: * serum creatinine clearance ≤ 60ml/min as estimated by cockroft-gault formula hematologic function: * the anc \< 1000/cmm, or platelet count \<50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy). * a patient will not be excluded because of pancytopenia ≥ grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies * baseline coagulopathy greater than or equal to grade 3 unless due to anticoagulant therapy. pulmonary function: * patients with \< 50% of predicted forced expiratory volume (fev1) or \<50% of predicted diffusing capacity for carbon monoxide (dlco), corrected for hemoglobin concentration and alveolar volume. note: patients with no prior history of pulmonary illness are not required to have pfts. fev1 will be assessed after bronchodilator therapy. recent prior therapy: * cytotoxic chemotherapy, corticosteroids (except stable doses of prednisone), whole body electron beam radiation therapy, hormonal, biologic or other standard or any investigational therapy of the malignancy for 3 weeks prior to entry into the trial * less than or equal to 1 month prior monoclonal antibody therapy (i.e. rituximab) * patients who are receiving or have received radiation therapy less than 3 weeks prior to study entry will be not be excluded providing the volume of bone marrow treated is less than 10% and also the patient has measurable disease outside the radiation port * any history of prior pseudomonas-exotoxin immunotoxin (pe) administration.